Abstract
BackgroundAs the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures.Methodology/Principal FindingsHere we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis.Conclusions/SignificanceCollectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation.
Highlights
The elaboration of class specific dendritic architectures is a hallmark of neuronal subtype as well as a key determinant in neuronal connectivity and the formation of functional neural networks
Our analyses demonstrate that Trio functions in promoting and refining class specific dendritic arborization patterns via GEF1- and GEF2-dependent interactions with Rac1 and Rho1, respectively
We demonstrate that Trio is required in mediating Cut induced effects on dendritic branching and filopodia formation suggesting that these molecules may operate in a common pathway to direct dendritic morphogenesis
Summary
The elaboration of class specific dendritic architectures is a hallmark of neuronal subtype as well as a key determinant in neuronal connectivity and the formation of functional neural networks. The Rho-family of small GTPases, including Rac, Rho, and Cdc, as well as certain downstream effectors, have been demonstrated to play a pivotal role in regulating actin dynamics during dendrite and dendritic spine morphogenesis [8,9,10,11,12] and defects in Rho GTPase signaling have been implicated in various forms of mental retardation [13] These small GTPases exert differential effects on neuron development with activation of Rac and Cdc functioning to promote neurite extension, whereas RhoA/Rho activation mediates neurite retraction. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures
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